Technetium-99m sestamibi scintigraphy for the assessment of lower extremity ischaemia in peripheral arterial disease

Technetium-99m sestamibi was used for functional investigation of the muscle perfusion of lower extremities in 35 patients with peripheral vascular disease. The aim was to test what useful information could be obtained by additional imaging of the legs in patients referred for risk stratification with dipyridamole myocardial scanning. Posterior images were acquired over the thighs and calves after postocclusive reactive hyperaemia and at rest. Inter- and intraextremity ratios and differences between the stress and rest data were used for the assessment of abnormal circulation. Arteriography was performed in every case, and surgical procedures or transluminal angioplasty in 31 patients. To estimate diagnostic accuracy, the results of^99mTc-sestamibi scintigraphy were compared with those of angiography and the functional consequences of revascularization procedures. The sensitivity and specificity of^99mTc-sestamibi scintigraphy were 55% and 25%, respectively, with an overall accuracy of 50%. Apparently methodological error was not responsible for these poor results. Instead, a paradoxically high uptake of the radiopharmaceutical in muscles supplied by significantly stenosed vessels was identified as the main source of both false-negative and false-positive results. This phenomenon resembles the findings of a previous study involving delayed administration of thallium-201 after exercise. In conclusion,^99mTc-sestamibi scintigraphy has not proved sufficiently reliable to help in the management strategy for patients with peripheral vascular disease.     

Improved cytosolic free calcium mobilization and superoxide production in bicarbonate-based peritoneal dialysis solution

Background. Intraperitoneal phagocytes play an important role in local host defence to prevent CAPD peritonitis. The intracellular calcium [Ca²⁺]i is thought to be involved in the regulation of various cell functions. This study therefore investigates the effect of lactate-based dialysis solution (LBDS) and bicarbonate-based dialysis solution (BBDS) on cytosolic free calcium mobilization and superoxide production (SP) as important steps in signal transduction and bacterial killing. Methods. We studied changes in [Ca²⁺]i and SP following stimulation with N-formyl-methionyl-leucyl-phenylalanine (fMLP) in polymorphonuclear neutrophils (PMNs) incubated in either LBDS-pH 5.2, LBDS adjusted to pH 7.4, 1:10 diluted spent and fresh LBDS or BBDS-pH 7.4 with different glucose concentrations, comparing the data with cells treated with Hanks buffer (HBSS) pH 7.4 as control. To elucidate the effect of glucose and lactate PMNs were additionally incubated in HBSS-pH 7.4, containing glucose (HBSS-Glu-pH 7.4) or lactate (HBSS-Lact-pH 7.4) in the same concentrations as contained in CAPD solutions and tested as above. PMNs were isolated from healthy blood donors and incubated with dialysis solution 10 min prior to stimulation with fMLP. Results. [Ca²⁺]i mobilization and SP were completely inhibited in PMNs incubated in LBDS pH 5.2. pH adjustment of LBDS to 7.4 and 1:10 dilution of spent and fresh LBDS corrected some of the suppression of the calcium influx and superoxide production. BBDS pH 7.4, however, preserved physiological cell function significantly better at low (1.5 and 2.3%) glucose concentrations. Conclusion. In comparison to conventional lactate-based dialysis solution, pH adjusted and 1:10 diluted LBDS, bicarbonate-based dialysis solution is more biocompatible since it preserves significantly better neutrophil cell functions.     

Analgesic nephropathy in Hungary: the HANS study.

BACKGROUND: The diagnosis of analgesic nephropathy has improved significantly with modern imaging techniques. We reviewed a large portion of the Hungarian dialysis population to obtain additional insight into the problem. METHODS: Twenty-two participating dialysis units enrolled 1400 patients on renal replacement therapy between 1 January 1995 and 1 January 1998. Patients with no known aetiology (n = 284) were interviewed and studied with renal imaging. We assessed the presence of decreased renal mass combined with either bumpy contours, papillary calcification, or both. The subjects studied were interrogated extensively. RESULTS: Our survey suggested analgesic nephropathy in 47 of 1400 patients (3.3%), 3-fold higher than the EDTA database estimate for Hungary. The analgesics most commonly abused were phenacetin-containing mixtures. The driving symptoms were mainly headache and joint pain. Cardiovascular complications were more common than in the rest of the dialysis population, independent of smoking and lipid values (P<0.01). CONCLUSIONS: Phenacetin should be banned. Our study results support the need for longitudinal cohort and case-control studies in Hungary.     

Short communication: treatment of relapsing-remitting multiple sclerosis 96 patients with IFN-beta1b: results of a 6-year follow-up.

The first pharmacon with proved efficacy for the treatment of patients with the relapsing-remitting or relapsing-progressive form of multiple sclerosis (MS) was interferon-beta1b (IFN-beta1b). In 1996, we started treating 34 relapsing-remitting (RRMS) and 2 relapsing-progressive MS (RPMS) patients with IFN-beta1b. Of these 36 patients, 28 received continuous medication for 6 years. The primary end point of the study was the effect of 6 years of continuous IFN-beta1b treatment on the annual relapse rate, the secondary end point was the change in the progression index during the 6 years, and the tertiary end point was the alteration in the expanded disability status scale (EDSS) score of the patients. Finally, we give the reasons for the dropouts. The relapse rate decreased by 80.62% (p < 0.001), the mean EDSS score increased significantly, by approximately 0.5 points, to 2.21 +/- 1.48 (p = 0.016), and the reduction in the mean progression index was 67.19% (p < 0.001). This increase of < 0.5 point in the EDSS score is appreciably different from the 3-point deterioration expected after 6 years for the natural course of the disease. The significant improvement in the progression index clearly demonstrates that 6 years of IFN-beta1b therapy slowed the progression of the disease, thereby improving the quality of life of these MS patients.     

Twenty-four-hour ambulatory blood pressure profiles in pediatric patients after renal transplantation

Ambulatory blood pressure monitoring was applied in 27 pediatric patients aged 6.3 – 24.3 (median 15.0) years who had been transplanted 1.5 – 8.4 years previously. Daytime values were compared with the mean of 10 concomitant casual blood pressure recordings. At the time of the study, antihypertensive drugs were given to 17 patients. Inulin clearance ranged from 18 to 116 (median 66) ml/min per 1.73 m². Ambulatory blood pressure monitoring confirmed hypertension or normotension determined by casual blood pressure measurements in 63% of patients. The physiological nocturnal dip in blood pressure was attenuated or reversed in 8 of 27 patients. It was reduced in all 3 patients with renal artery stenosis of the graft, in 3 of 4 patients with chronic rejection, in the only patient with recurrent focal segmental glomerulosclerosis, and in 1 of 6 patients with past acute rejection. The dipping was not related to inulin clearance. In conclusion, casual blood pressure measurements do not accurately reflect blood pressure in pediatric patients transplanted more than 1.5 years previously. A reduced nocturnal dip in blood pressure may indicate an underlying renovascular or renoparenchymal pathology. Ambulatory blood pressure monitoring should regularly be applied in patients with renal transplants. Received May 23, 1995; received in revised form June 18, 1996; accepted June 20, 1996     

Mycobacterium ulcerans cytotoxicity in an adipose cell model

An adipose cell (SW872) model was developed to observe cellular necrosis and apoptosis upon Mycobacterium ulcerans infection and treatment with mycobacterial exudate. Apoptosis was likely due to secreted proteins, while necrosis was likely due to mycolactone. Our data suggest that additional factors in M. ulcerans may be involved in Buruli ulcer pathogenesis.     

Coding assignments of Drosophila X virus genome segments: in vitro translation of native and denatured virion dsRNA

Both dsRNA genome segments of Drosophila X virus (DXV) were denatured and translated in vitro using nuclease-treated rabbit reticulocyte lysates. The synthesis of all four primary gene products was detected by polyacrylamide gel electrophoresis and autoradiography. Genome segment A (mol wt 2.3 X 10(6)) encoded polypeptides with molecular weights of 67,000 (67K), 34K, and 27K, whereas segment B (mol wt 22 X 10(6)) encoded the 110K polypeptide. The proteolytic processing of 67K which generates a 49K polypeptide in infected cells was also observed in vitro. Pulse-chase experiments indicated that synthesis of the three polypeptides encoded by genome segment A initiated independently and simultaneously, suggesting that segment A is polycistronic. Native (undenatured) DXV dsRNA could also be translated with high fidelity (vitro). The messenger activity of native dsRNA was abolished by S1 nuclease treatment but completely restored on subsequent denaturation. In vitro "pulse-chase" experiments using native dsRNA as messenger, indicated that the order of translation of polypeptides on genome segment A was 5'-67K-27K-34K-3'.     

Transmission disequilibrium tests confirm the link between DRD4 gene polymorphism and infant attachment.

Following up the results of a previous population association study (Lakatos et al. [2000: Mol Psychiatry 5:633-637; Lakatos et al. [2002: Mol Psychiatry 7:27-31]) by analyses based on parental genetic data confirmed the link between infant attachment and the dopamine D4 receptor (DRD4) gene. Extended transmission disequilibrium tests (ETDT) were performed to determine whether biased transmission of exon III 48 basepair repeat alleles occurred to infants displaying disorganized and secure attachment behavior with their mothers. The overall allele-wise TDTs were significant for both groups (P = 0.038 and 0.020, respectively): a trend for preferential transmission of the seven-repeat allele to disorganized infants was observed (TDT(chi)(2) = 3.27, df = 1, P = 0.071), and there was a significant non-transmission of the same allele to securely attached infants (TDT(chi)(2) = 6.00, df = 1, P = 0.014). Analysis of haplotypes of the exon III repeat and the -521 C/T promoter polymorphisms in family trios showed that the transmission bias in the larger secure group was due to the low-rate transmission of the T.7 haplotype containing both the seven-repeat and the -521 T alleles (TDT(chi)(2) = 4.46, df = 1, P = 0.035). This suggests that not carrying the T.7 haplotype of the DRD4 gene may act as a resilience factor in the optimal development of early attachment.     

Con A activates an Akt/PKB dependent survival mechanism to modulate TCR induced cell death in double positive thymocytes

While low avidity ligation of the T cell receptor (TCR) leads to positive selection and further maturation of developing thymocytes providing the immune system with mature CD4(+) and CD8(+) (single positive) T cells, high avidity ligation triggers negative selection by apoptotic cell death and therefore the TCR repertoire is purged of autoreactive T cells. On peripheral T cells, however, high avidity ligation of the TCR triggers activation and survival not death. In the present study we used concanavalin A (Con A) and alpha-CD3 epsilon antibody to investigate a possible survival mechanism in connection with TCR ligation. Con A and alpha-CD3 epsilon were used in the study for the following reasons: (1) they both mimic the effects of high avidity TCR ligation by activating peripheral T cells, and (2) they trigger distinctively different physiological changes in developing thymocytes. While Con A supports events associated with cellular survival, alpha-CD3 epsilon induces apoptotic cell death. In our experimental system the TCR was cross-linked by Con A and alpha-CD3 epsilon in thymocytes of major histocompatibility complex (MHC) deficient thymus organ cultures, where signals from the TCR can be triggered on zero background signal level. We have found that TCR cross-linking by Con A and not by alpha-CD3 epsilon decreases the gene and protein expression of the pro-apoptotic molecule, Bad; and that Con A is capable of the activation of the survival signalling pathway including protein kinase B (Akt/PKB) independently of phosphatidyl inositol kinase (PI3K).